Weyl asymptotics for magnetic Schr\"odinger operators and de Gennes' boundary condition

This paper is concerned with the discrete spectrum of the self-adjoint realization of the semi-classical Schr\"odinger operator with constant magnetic field and associated with the de Gennes (Fourier/Robin) boundary condition. We derive an asymptotic expansion of the number of eigenvalues below the essential spectrum (Weyl-type asymptotics). The methods of proof relies on results concerning the asymptotic behavior of the first eigenvalue obtained in a previous work [A. Kachmar, J. Math. Phys. Vol. 47 (7) 072106 (2006)].Comment: 28 pages (revised version). to appear in Rev Math Phy

Conivaptan: a step forward in the treatment of hyponatremia?

Hyponatremia is one of the most common electrolyte abnormalities linked to adverse outcomes and increased mortality in hospitalized patients. While the differential diagnosis for hyponatremia is diverse, most cases stem from arginine vasopressin (AVP) dysregulation, where hypoosmolality fails to suppress AVP synthesis and release. The physiological effects of AVP are currently known to depend on its interaction with any of 3 receptor subtypes V1A, V2, and V1B. Activation of V2 by AVP is the key in renal water regulation and maintenance of total body volume and plasma tonicity. Despite the long-recognized problem with excess AVP in euvolemic and hypervolemic hyponatremia, traditional therapeutic options have relied on nonspecific and potentially problematic strategies. More recently, a new class of drugs, introduced as “aquaretics,” has gained great attention among clinicians because of its ability to correct hyponatremia via direct competitive inhibition of AVP at V2 receptors to induce renal electrolyte-free water excretion. In this paper, we aim to review available clinical data on the only FDA-approved aquaretic, dual V1A/V2 receptor antagonist conivaptan, discuss its clinical indications, efficacy, safety profile, and comment on its clinical limitations

Implant-supported fixed and removable prostheses in the fibular mandible

Abstract Background To restore the health-related quality of life (HRQoL) of patients who underwent jaw resection and reconstruction surgery, dental rehabilitation is an essential procedure and also one of the most challenging for oral and maxillofacial surgeons. Even though recent studies have reported the possibility and reliability of dental implant rehabilitation with the fibula free flap (FFF), clinical reports of long-term follow-up cases are scarce. We herein reported seven cases of FFF reconstruction and implant rehabilitation. We also discussed implant planning strategy and surgical techniques. Methods From 2012 to 2019, seven patients were treated with FFF reconstructive jaw surgery combined with dental implant installation and fabrication of implant-supported prostheses at Seoul National University Dental Hospital, Seoul, Korea. Patient characteristics and FFF treatment results were collected. Records of dental implants were analyzed clinically and radiologically. Results Among the seven patients in this report, there were three males and four females, with an average age of 54.4 years. A total of 39 implants were placed in the fibular bone. The mean follow-up period after implant installation was 24 months. Five implants failed and were removed 3 months after installation. The implant success rate was 87.2%. Marginal bone loss at 12 months after loading was 0.23 ± 0.18 mm on the mesial side and 0.25 ± 0.26 mm on the distal side. Conclusion With the challenges present in FFF-reconstructed patients, an implant-supported prosthesis is a reliable option for stable and functional oral rehabilitation. The implant-supported prosthesis on the FFF has great results regarding restoration of function (mastication, swallowing, and speaking), appearance, and overall HRQoL. Collaboration between surgeons and prosthodontists is essential for a satisfying outcome

Clinical feasibility and benefits of a tapered, sand-blasted, and acid-etched surfaced tissue-level dental implant

Abstract Background It has been 50 years since Brånemark first introduced the concept of osseointegration. Since then, numerous ongoing research, developments, and optimization of implant properties have been conducted. Despite the high survival and success rates of dental implants, failures still occur in a small number of patients that are being rehabilitated by implants. The purpose of this study was to evaluate the survival and success rate of the Stella® implants that incorporate sand-blasted and acid-etched (S&E) surface treatment and tapered body design to confirm their clinical feasibility and benefits after placement. Methods We reviewed 61 partially and fully edentulous patients who underwent a tapered, S&E surfaced tissue-level implant placement between May 2013 and February 2016 in the Department of Oral and Maxillofacial Surgery in the Seoul National University Dental Hospital. Patient characteristics and treatment results were collected, and records of dental implants were analyzed clinically and radiologically. Results A total of 105 implant fixtures were placed in these patients. The mean age at the time of the surgery was 63.7 years with a range of 31 to 88 years. In total, 4.0-mm and 4.5-mm diameter implants were the most frequently used dental implants (40%, 49%) in this study. Implants 8.5 mm in length were predominantly used (60%). Seventy dental implants were placed in the mandible (70%), and only one dental implant was placed in the maxillary anterior region. At the end of the 5-year observation period, the success rate of the Stella® implants was 98.1%. Among the 105 implants placed, 2 were considered to be failures. Summarizing the clinical and radiographic results, the remaining 103 implants were considered successfully integrated. Conclusion The overall success rate was 98.1%. The tapered, S&E surfaced tissue-level implant system exhibited great performance in a variety of clinical situations including failed implant sites that enabled predictable and successful treatment outcomes. The effectives of a tapered design of tissue level, not a parallel design, are shown in this clinical report

Whole-genome analysis of a daptomycin-susceptible Enterococcus faecium strain and its daptomycin-resistant variant arising during therapy

Development of daptomycin (DAP) resistance in Enterococcus faecalis has recently been associated with mutations in genes encoding proteins with two main functions: (i) control of the cell envelope stress response to antibiotics and antimicrobial peptides (LiaFSR system) and (ii) cell membrane phospholipid metabolism (glycerophosphoryl diester phosphodiesterase and cardiolipin synthase [cls]). However, the genetic bases for DAP resistance in Enterococcus faecium are unclear. We performed whole-genome comparative analysis of a clinical strain pair, DAP-susceptible E. faecium S447 and its DAP-resistant derivative R446, which was recovered from a single patient during DAP therapy. By comparative whole-genome sequencing, DAP resistance in R446 was associated with changes in 8 genes. Two of these genes encoded proteins involved in phospholipid metabolism: (i) an R218Q substitution in Cls and (ii) an A292G reversion in a putative cyclopropane fatty acid synthase enzyme. The DAP-resistant derivative R446 also exhibited an S333L substitution in the putative histidine kinase YycG, a member of the YycFG system, which, similar to LiaFSR, has been involved in cell envelope homeostasis and DAP resistance in other Gram-positive cocci. Additional changes identified in E. faecium R446 (DAP resistant) included two putative proteins involved in transport (one for carbohydrate and one for sulfate) and three enzymes predicted to play a role in general metabolism. Exchange of the “susceptible” cls allele from S447 for the “resistant” one belonging to R446 did not affect DAP susceptibility. Our results suggest that, apart from the LiaFSR system, the essential YycFG system is likely to be an important mediator of DAP resistance in some E. faecium strains

Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt

Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in Enterococcus faecalis.

Bacteria have developed several evolutionary strategies to protect their cell membranes (CMs) from the attack of antibiotics and antimicrobial peptides (AMPs) produced by the innate immune system, including remodeling of phospholipid content and localization. Multidrug-resistant Enterococcus faecalis, an opportunistic human pathogen, evolves resistance to the lipopeptide daptomycin and AMPs by diverting the antibiotic away from critical septal targets using CM anionic phospholipid redistribution. The LiaFSR stress response system regulates this CM remodeling via the LiaR response regulator by a previously unknown mechanism. Here, we characterize a LiaR-regulated protein, LiaX, that senses daptomycin or AMPs and triggers protective CM remodeling. LiaX is surface exposed, and in daptomycin-resistant clinical strains, both LiaX and the N-terminal domain alone are released into the extracellular milieu. The N-terminal domain of LiaX binds daptomycin and AMPs (such as human LL-37) and functions as an extracellular sentinel that activates the cell envelope stress response. The C-terminal domain of LiaX plays a role in inhibiting the LiaFSR system, and when this domain is absent, it leads to activation of anionic phospholipid redistribution. Strains that exhibit LiaX-mediated CM remodeling and AMP resistance show enhanced virulence in the Caenorhabditis elegans model, an effect that is abolished in animals lacking an innate immune pathway crucial for producing AMPs. In conclusion, we report a mechanism of antibiotic and AMP resistance that couples bacterial stress sensing to major changes in CM architecture, ultimately also affecting host-pathogen interactions

A multidisciplinary approach to estimating wolf population size for long-term conservation

The wolf (Canis lupus) is among the most controversial of wildlife species. Abundance estimates are required to inform public debate and policy decisions, but obtaining them at biologically relevant scales is challenging. We developed a system for comprehensive population estimation across the Italian alpine region (100,000&nbsp;km2), involving 1513 trained operators representing 160 institutions. This extensive network allowed for coordinated genetic sample collection and landscape-level spatial capture–recapture analyses that transcended administrative boundaries to produce the first estimates of key parameters for wolf population status assessment. Wolf abundance was estimated at 952 individuals (95% credible interval 816–1120) and 135 reproductive units (i.e., packs) (95% credible interval 112–165). We also estimated that mature individuals accounted for 33–45% of the entire population. The monitoring effort was spatially estimated thereby overcoming an important limitation of citizen science data. This is an important approach for promoting wolf–human coexistence based on wolf abundance monitoring and an endorsement of large-scale harmonized conservation practices